INVESTIGATION OF HUMAN DISEASE Essay Example | Topics and Well Written Essays - 1000 words

INVESTIGATION OF HUMAN DISEASE - Essay ExampleAlternatively, a shorted dystrophin gene may be expressed precisely still different from everyday due to an modify molecular weight. Different probes against different parts of the gene, or alternatively gene sequencing, target be exploit to identify the missing parts. Given the almost asymptomatic patients status, likely due to the young age, no histological features are expected in muscle biopsies. Therefore, a molecular, i.e. immuno-histochemical, analysis will be necessary. Indeed, immunofluorescence (IF) analysis for dystrophin can confirm the genotyping. In physiological conditions, laminin is localized around all muscle fibers and it appears as circles/polygonal shapes in muscle cross-sections, while it is absent in virtually all muscle fibers in diseased individuals (with the notability exception of possible revertant fibers). Given the invasive nature of this procedure, the IF analysis, which requires more tissue to be coll ected, will be performed as a second option and only in the presence of positive genetic tests. On examining the genomic DNA it was found that exon 52 was absent. (b) Will splicing of exon 51 to 53 convey a functional shortened dystrophin? Explain and justify your decision by using an illustration and text (20%). The splicing of exon 51 to 53 does not produce a shortened dystrophin, since the two exons excite different codon boundary. The result of the exon 52 deletion, is thus disruption of the genetic code and the premature hold of protein translation. On the contrary, the splicing of exon 51 to 54 would give rise to a shortened but functional form of dystrophin (see diagram below). In the case presented above, the absence of dystrophin expression and the development of DMD is the diagnosis. Scheme of exon boundary extremities in the dystophin region of interest After genetic counselling the parents choose to seek do from a specialist in gene therapy. (c) If you were the gene therapy specialist what kind of therapy would you suggest for the boy. Justify your choice. (20%) I would suggest an exon skipping approach with antisense oligonucleotides (AON) aimed to skip exon 53. The loss of the latter in addition to the immanent loss of exon 52 will likely allow to rescue the expression of an almost normal dystrophin, which lacks only two of the repeated motifs that constitute the central body of the protein. Exon skipping has recently been proven an expeditious therapeutic approach in large animals (dogs) affected by muscular dystrophy (Yokoda, 2011). PART II (50% total) 1) The picture above shows a family with an inherited disorder. All affected individuals are tall and thin, with long fingers and toes. a) What would a genetic counselor be able to tell an affected individual about the mode of hereditary pattern and the serious complications associated with the disorder (10%) The phenotype of the people in the picture is compatible with the diagnosis of t he Marfan. In fact, people with Marfan syndrome tip to be unusually tall, with long, thin fingers. It is inherited as a dominant trait, thus people who confuse inherited one affected gene from either parent will have Marfan syndrome. This may inform the high penetrance of the disease into a group of individuals, likely members of the same family in the pcture. b) Explain the molecular fanny of the condition (15%)